Related Experiment Video

Updated: Oct 21, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.0K

Mechanisms of gefitinib-induced QT prolongation

Ling-Jun Jie1, Yun-Da Li1, He-Qiang Zhang1

  • 1Xiamen Cardiovascular Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361004, China.

European Journal of Pharmacology
|September 2, 2021
PubMed

Insights

Gefitinib, a targeted therapy for non-small cell lung cancer, prolongs the QT interval by blocking the hERG channel. This cardiac effect necessitates caution during treatment.

Area of Science:

  • Cardiology
  • Pharmacology
  • Oncology

Background:

  • Gefitinib is a targeted therapy for non-small cell lung cancer (NSCLC).
  • The human Ether-à-go-go-Related Gene (hERG) channel is crucial in cardiac repolarization and a target in drug-induced long QT syndrome.
  • The potential for gefitinib to induce QT interval prolongation remained unclear.

Purpose of the Study:

  • To investigate the electrophysiological effects of gefitinib on cardiac ion channels.
  • To determine if gefitinib can induce QT interval prolongation.
  • To elucidate the mechanism by which gefitinib affects cardiac repolarization.

Main Methods:

  • Whole-cell patch-clamp technique was used to assess gefitinib's effects on various potassium currents (IKr, IKs, Ito, IK1) and action potentials in guinea pig ventricular myocytes.
  • Langendorff heart perfusion technique was employed to evaluate gefitinib's impact on the electrocardiogram (ECG).

Main Results:

  • Gefitinib potently inhibited the rapidly-activating delayed rectifier potassium current (IKr) by blocking the hERG channel in a concentration-dependent manner (IC50 = 1.91 μM).
  • Gefitinib demonstrated pore inhibition of hERG channels, with reduced efficacy at specific hERG mutants.
  • Gefitinib altered hERG channel kinetics, accelerating inactivation and decreasing steady-state inactivation. It also inhibited the slowly-activating delayed rectifier potassium current (IKs) (IC50 = 23.8 μM).
  • Gefitinib dose-dependently increased action potential duration (APD) in ventricular myocytes and prolonged the corrected QT interval (QTc) in isolated hearts.

Conclusions:

  • Gefitinib prolongs the QTc interval primarily through potent blockade of the hERG channel and modulation of its kinetic properties.
  • Partial blockade of KCNQ1/KCNE1 channels may also contribute to the delayed repolarization and prolonged QT interval.
  • Caution is advised when using gefitinib for NSCLC treatment due to its potential to cause QT interval prolongation.
Keywords:
Action potentialCorrected QT intervalGefitinibHuman ether-à-go-go-related gene potassium channel

More Related Videos

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation08:03

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation

Published on: October 20, 2022

2.0K
High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers14:03

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers

Published on: March 24, 2023

2.1K

Related Concept Videos

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.4K
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
368
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
37
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
845
Antiepileptic Drugs: GABAergic Pathway Potentiators01:18

Antiepileptic Drugs: GABAergic Pathway Potentiators

γ-aminobutyric acid or GABA, plays a pivotal role as an inhibitory neurotransmitter in the brain. GABA pathway potentiators, also known as GABAergic drugs, are a class of pharmaceutical agents designed to enhance the functioning of the GABAergic system. These medications primarily treat epilepsy, a neurological disorder characterized by recurrent seizures.
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for...
813
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
1.2K